Review of living kidney donor outcomes, in The Lancet

In The Lancet
Volume 385, Issue 9981, 16–22 May 2015, Pages 2003–2013

Living kidney donation: outcomes, ethics, and uncertainty
Dr Peter P Reese, MD,  Prof Neil Boudville, MD, Prof Amit X Garg, MD

Here's the summary:
"Since the first living-donor kidney transplantation in 1954, more than half a million living kidney donations have occurred and research has advanced knowledge about long-term donor outcomes. Donors in developed countries have a similar life expectancy and quality of life as healthy non-donors. Living kidney donation is associated with an increased risk of end-stage renal disease, although this outcome is uncommon  (less than .5 percent increase in incidence at 15 years). Kidney donation seems to elevate the risks of gestational hypertension and pre-eclampsia. Many donors incur financial expenses due to factors such as lost wages, need for sick days, and travel expenses. Yet, most donors have no regrets about donation. Living kidney donation is practised ethically when informed consent incorporates information about risks, uncertainty about outcomes is acknowledged when it exists, and a donor's risks are proportional to benefits for the donor and recipient. Future research should determine whether outcomes are similar for donors from developing countries and donors with pre-existing conditions such as obesity."


And this...
"In many countries, living kidney donation is the only affordable treatment for kidney failure. This is evident across large regions of India and Pakistan, for example, where chronic dialysis is rationed in units supported by government or community donations, or is only available with payments that are prohibitive for most patients. In this respect, chronic dialysis is viewed as a bridge to a life-saving kidney transplant from a living donor. In many developing countries, the infrastructure to procure deceased-donor organs does not exist.

"Unrelated and incompatible donors
Living kidney donation in unrelated donors (eg, friends, spouses, or distant relatives of the recipient) are becoming more common. In the USA, the proportion of living kidney donations from unrelated donors increased from 30% to 57% between 1999 and 2013. Similar trends are evident in Europe, Australia, and New Zealand.

"This rise in unrelated living kidney donation is largely associated with a declining emphasis on close HLA matches between donor–recipient pairs. With advances in immunosuppressive therapy, the longevity and function of the transplanted organ is now less dependent on the genetic donor–recipient relationship than in the past. The rise in unrelated donors has also been helped by so-called kidney paired donation, a strategy used to overcome donor–recipient incompatibility if the transplant candidate has antibodies to the donor's blood or HLA type. Such antibodies greatly increase the risk of donated-organ rejection and, in the case of anti-HLA antibodies, might develop because of previous pregnancies, blood transfusions, or transplants. As shown in figure 2, registries of incompatible donor–recipient pairs have enabled transplantation to proceed through paired exchanges, or donation chains in which each donor provides a kidney to an unrelated compatible recipient. Paired exchange has been helped by the transportation of living-donor kidneys between centres and by non-synchronous transplants, in which one or more donors wait to donate until new pairs enter the chain. In some cases, a transplantation chain begins when an individual with no relationship to any recipient donates a kidney (termed non-directed donation). In 2012, this type of altruistic donation enabled a 30-transplant chain to proceed."

Kidney exchange in Australia, 2011

Two reports about transplantation in Australia are now available for 2011:

The 2011 Organ Donation and Transplantation Performance Report is available at www.donatelife.gov.au/the-authority/performance-reports.

The 2011 Report from the Australian and New Zealand Organ Donation Registry is available at www.anzdata.org.au.

The first of those includes the following:

"The Australian Paired Kidney Exchange (AKX) Program commenced in late 2010. The AKX Program complements existing living kidney donor programs, and provides an opportunity for transplant to those patients who are unlikely to receive a transplant through standard programs, due to their highly sensitised antibody status.

"2011 saw a significant expansion of the AKX Program, resulting in 23 additional kidney transplants. Eight (35%) of those Australians who received an AKX transplant had less than a 1 in 10 chance to receive a kidney as part of standard donation/transplantation programs.

"The success rate of 23 actual transplants, from the initial 39 possible transplants in Australia, was one of the highest in the world in 2011.

"The 16 individuals who did not progress to transplant did not proceed for clinical reasons."

A long non-directed donor chain in Australia

Here's the story fro;m the Melbourne Herald Sun (with nice pictures):
IN AN incredible medical marathon, a dozen Victorians went under the knife in ­Australia’s largest live kidney ­donation and transplant swap.

"The Australia-first paired ­kidney exchange, if successful, will give six people who have been languishing on dialysis a second chance of life.

"Twelve operations to remove and transplant the organs were performed in four major hospitals across Melbourne yesterday.

"The extraordinary chain of events was triggered by Victoria’s first altruistic donor giving a ­kidney up to a stranger.

"That selfless act set off a domino effect that became the ­nation’s first six-way paired kidney transplant exchange attempt.

"Five other Victorians gave up a kidney to a suitably matched stranger.

"A loved one of each donor who was in need of a kidney received a donated organ in return."

A logistically complicated 14-person kidney exchange chain in Australia--with an aircraft failure--but a happy ending

There was an aircraft failure while one of the kidneys was being shipped:

One altruistic donor, six hospitals hundreds of specialists and seven transplant patient lives saved

"All 14 patients involved in Australia’s first seven-way paired kidney swap have ­recovered well after the transplants at Victoria’s Monash Medical Centre and Royal Melbourne and Austin hos­pitals, in co-ordination with NSW’s Westmead, Prince of Wales and John Hunter ­hospitals.

For five anxious hours, the team battled to overcome a “hiccup” when a malfunctioning aircraft was forced to return to Sydney mid-flight with a Melbourne-bound kidney, but still managed to complete the operations safely on ­November 19.

After three months’ planning, Australian Paired Kidney Exchange Program director Professor Paolo Ferrari said the transplants were “an amazing team effort”.

“It is always an effort when you have two, three, four or, in this case, seven,” Prof Ferrari said.

“Although this ­occurred recently, the actual match-up that told us there was a possibility for these ­patients to have a kidney transplant first came in ­August. Because of the excitement on that day — mostly ­because of the complexity of having all the centres involved and the little hiccup — there was a lot of tension.
...
"At 8am, simultaneous operations began in seven operating theatres in the three Melbourne and three Sydney hospitals, as the first stage to remove the kidneys from the donors.

The second-stage ­operations began at a Melbourne hospital at 12.23pm when an organ couriered across town was taken off the ice and implanted into a lucky recipient.

Five other synchronised transplants occurred progressively across the two cities over the afternoon as the kidneys arrived via Qantas flights and StarTrack couriers.

But a problem with an ­anaesthetic machine delayed one Sydney retrieval and the kidney had to be placed on a flight 30 minutes later than planned.

The problem was compounded when the aircraft developed its own issues mid-flight and had to return to Sydney with its precious cargo.

Five hours later, the kidney finally arrived in Melbourne still in good health, where the Austin Hospital team led by Associate Professor Frank Ierino was able to begin the final transplant at 9.30pm."

Kidney Paired Donation in Developing Countries: a Global Perspective

 Vivek Kute and his colleagues argue that one of the lessons from the developing world is that kidney exchange can save many lives, but may need to be organized differently in some ways than in the developed world.

Kidney Paired Donation in Developing Countries: a Global Perspective by Vivek B. Kute, Vidya A. Fleetwood, Sanshriti Chauhan, Hari Shankar Meshram, Yasar Caliskan, Chintalapati Varma, Halil Yazıcı, Özgür Akın Oto & Krista L. Lentine, Current Transplantation Reports (2023)  (here's a link that may provide better access]

Abstract

...

"Despite the advantages of KPD programs, they remain rare among developing nations, and the programs that exist have many differences with those of in developed countries. There is a paucity of literature and lack of published data on KPD from most of the developing nations. Expanding KPD programs may require the adoption of features and innovations of successful KPD programs. Cooperation with national and international societies should be encouraged to ensure endorsement and sharing of best practices.

Summary

KPD is in the initial stages or has not yet started in the majority of the emerging nations. But the logistics and strategies required to implement KPD in developing nations differ from other parts of the world. By learning from the KPD experience in developing countries and adapting to their unique needs, it should be possible to expand access to KPD to allow more transplants to happen for patients in need worldwide."

...

" Despite the advantages of KPD programs, they remain rare in the developing world, and the programs that exist have many differences with those of developed countries. Program structure is one of these differences: multi-center, regional, and national KPD programs (Swiss, Australia, Canada, Dutch, UK, USA) are more common in the developed than the developing world, whereas single center programs are more common

...

"kidney exchanges frequently take weeks to months to obtain legal permission in India despite the fact that only closely-related family members (i.e., parents, spouse, siblings, children, and grandparents) are allowed to donate a kidney [47].

...

"Protecting the privacy of a donor, including maintaining anonymity when requested, is common practice among developed countries but uncommon in developing nations. Anonymous allocation during KPD is a standard practice in the Netherlands, Sweden, and other parts of Europe, but this is not the case in countries such as India, Korea, and Romania [14, 48, 49]. In areas where anonymity is not maintained, the intended donor/recipient pair must meet and share medical information once a potential exchange is identified, but before formal allocation of pairs occurs. The original donor/ recipient pair may refuse the proposed exchange option for any reason and continue to be on the waitlist. In India, nonanonymous KPD allocation is standard practice and has the goal of increasing trust and transparency between the transplant team and the administrative team [14, 49]. Countries differ in philosophical approaches to optimizing trust and transparency, and objective data on most effective practices would benefit the global community."

********

Tomorrow I hope to have a few words to say about the equally unique situation in China.

######

Update:

Tuesday, September 19, 2023

Organ transplantation in China: in transition--and controversy about paying funeral costs

A non-directed donor kidney exchange chain in Australia

Here's a heartwarming longish story about a longish kidney exchange chain in Australia:
7 kidney donors, 7 recipients, 6 hospitals, 3 cities. What could possibly go wrong?  Medical ingenuity and the kindness of a stranger brought together 14 people in a life-changing event.

February 20, 2016

Australia's parliament reports on organ trafficking

Australia's parliament has published a report on organ trafficking in Australia. They didn't find much trafficking there, but recommend that data be more vigorously collected. They report that only one case of (attempted) paid organ donation has come to the attention of the authorities, but that it was successfully prevented, and the intended recipient died. The report ends with a case study of an anatomical exhibit using human cadavers.

Compassion, Not Commerce:An Inquiry into Human Organ Trafficking and Organ Transplant Tourism

Human Rights Sub-Committee, House of Representatives, Joint Standing Committee on Foreign Affairs, Defence and Trade, November 2018, Canberra

(The above link is the the 178 page pdf version, and here's a link to the table of contents and each chapter separately).

"This report examines the global prevalence of human organ trafficking and the scope of Australian participation within this illicit trade.

...

"2.5...The commercial trade in human organs is near-universally prohibited. Despite these prohibitions and restrictions, the illicit commercial trade in human organs has been estimated by the research advisory organisation Global Financial Integrity to be worth between US$840 million and $1.7 billion globally each year.4 Up to 10 per cent of kidney transplants worldwide may now involve commercially traded organs.
...
"3.15 There has been only one reported case to date of alleged organ trafficking within Australian jurisdiction,
 Alleged case of organ trafficking in Australia
"In 2011, an Australian couple were alleged to have brought a woman from the Philippines to Australia, promising her monetary compensation and a working visa in exchange for a kidney donation.
The woman changed her mind upon arriving in Australia. Medical transplant integrity procedures – a pre-operative counselling session at a Sydney hospital –ensured that the situation was discovered before the removal of the organ.
The potential donor was identified as an alleged victim of organ trafficking, resulting in referral to the Australian Federal Police. Due to the death of the prospective recipient, and limitations of the legislation as then in force, the matter did not progress to prosecution."
...
"3.20 International studies have observed the tendency of patients born in a country where organ trafficking may occur, but living outside of that country, to be at a substantially higher risk of participation in transplant tourism.31 This would appear to be equally true in Australia, as Dr Campbell Fraser observed: "...less than five per cent of Australians who are waiting on organs are likely to even consider going overseas. ...most of the Australians who have purchased an organ overseas have ethnic family connections to the countries or regions where they buy their organs—Pakistani Australians tended to go to Pakistan, Egyptian Australians travel to Egypt, and so on."
...
"Mandatory reporting by medical practitioners
3.41 A large number of submissions and witnesses argued in favour of the establishment of a nationwide mandatory reporting scheme for commercial transplants. A Bill before the Parliament of New South Wales, Human Tissue Amendment (Trafficking in Human Organs) Bill 2016, introduced by Mr David Shoebridge MP, seeks to amend the Human Tissue Act 1983 (NSW). The amendment would, inter alia, require medical professionals to report to the NSW Secretary of Health any reasonable belief that a patient has received a commercial transplant or one sourced from a non-consenting donor.
...
"Case study on alleged human tissue trafficking 
‘Real Bodies’
6.1 The Real Bodies commercial anatomical exhibition, on display in Australia during the course of this inquiry, was brought to the attention of the  Sub-Committee by a number of witnesses and is illustrative of an apparent gap in the current legislation. The Real Bodies exhibition involves the commercial display of 20 plastinated human cadavers, and ‘over 200’ plastinated organs, embryos and foetuses.1
Allegations of the trafficking of organs and other human tissue
6.2Mr David Shoebridge MP of the New South Wales Parliament informed the Sub-Committee as to the nature of the exhibition:...
"[they] are real bodies ... they are displayed in quite grotesque circumstances—some of them literally sawn down the middle and presented as a human standing and divided in two so that you can look into the internal parts of them. There are pregnant women. There are multiple fetuses ... put on display for commercial gain ... it is a grossly exploitative process. The proprietors ... have been asked about the circumstances in which these bodies came into their possession, and they have been unable and unwilling to prove that any of the persons on display ever gave their consent."
**********

Here's an earlier post on repugnance to anatomical exhibits using cadavers:

Saturday, March 28, 2009, Markets for (viewing) bodies

Kidney exchange in Australia passes the 100 transplant mark

"In September the Paired Kidney Exchange Program reached the milestone of 100 transplants."

Here's the story, focused on a six-way chain:
Six-way kidney transplant boosts altruistic donor rates
by Lucie Van Den Berg, Herald Sun, November 22, 2014

Misc. kidney exchange

A nondirected donor chain in Israel, apparently the first: 1st-ever ‘domino triple kidney-pair exchange’ saves 3 lives

"Prof. Eitan Mor, who heads the transplant department, said that domino kidney exchanges have been performed in the US, Australia, Holland and Taiwan, with data banks to coordinate details of would-be donors and recipients to facilitate swaps. Now Israel, through Beilinson, has begun to build such a data bank, with Dr. Ruth Rahamimov and Rahel Michovitz in charge of it."

Organ markets, transplant tourism, and compensation of donors in Asia

The Australian ABC News carries a story about transplant tourism that seems to focus on China (but which I hope is a little dated): Australian organ tourists drive sinister trade
One of the disturbing (hearsay) quotes: ""I know of one patient who was heading for a country overseas; told the unit that they would be unable to come in for dialysis tomorrow because they were shooting her donor tomorrow."

The story quotes one Australian surgeon as suggesting that relying primarily on deceased donors would be preferable, since there is less room for an illegal market to creep in (maybe the reporter didn't read him the quote above).  Australia, like everywhere else in the world, doesn't have enough deceased donor kidneys to meet demand, and live donor transplantation continues to outperform deceased donor transplantation (hence kidney exchange). Stories like this make me worry about babies being thrown out with bathwater...

A recent paper discusses the organ trade in Asia, and policies regarding legal compensation of donors: , Living Organ Transplantation Policy Transition in Asia: towards Adaptive Policy Changes by Alex He Jingwei, Allen Lai Yu-Hung, and Leong Ching, in Global Health Governance, Volume III, Issue 2: Spring 2010.
The authors are all Ph.D. candidates at the Lee Kuan Yew School of Public Policy, National University of Singapore.

"This paper surveys trends in ten Asian economies and highlights the gradual loosening of restrictions on donor eligibility and compensation. We suggest that one explanation for those cases which have remained unchanged in their transplantation policies is the existence of a thriving trans-boundary organ trade, which although
ethically indefensible, is tolerated by pragmatic policymakers."
...
"...Saudi Arabia has changed its policy. According to the World Health Organization (WHO), a law passed in Saudi Arabia in October 2007 envisages that the government pays a monetary “reward” of 50,000 riyals (US$13,300) and other benefits, including life-time medical care, for unrelated organ donors in a system regulated at the national level. The law’s supporters said it would stop Saudi citizens from travelling to China, Egypt, Pakistan, the Philippines, and other countries to receive organ transplants.30 The effect of this new policy is immediate—Saudi Arabia quadrupled its rates of living kidney donation within a short period, ranking no. 1 today.31
"Singapore has faced a persistent shortage of organs for donations too. As of October 31, 2008, there were about 520 people on the kidney transplant waiting list. The average waiting time is nine years. Religious customs, cultural norms, and a fear of transplant operations have been cited as reasons for the donor shortage. Given its small population, and level of affluence, it is perhaps natural that this country will eventually find some ways to regulate this de facto market. The most recent of these has been an amendment to the “Human Organ Transplant Act” (HOTA) to allow compensation to donors. At the same time, it has also increased the penalty for organ trading, signaling that a complete price mechanism is unacceptable.
"HOTA originally prohibits the giving or acceptance of organs under a “contract of arrangement” which precludes organ trading. In November 2008, the Ministry of Health (MOH) proposed that paired matching for exchange of organs be allowed in Singapore to increase the chances of improved transplant outcomes and to save more lives. Under this arrangement, patients can essentially switch donors. The MOH sees this as creating matches that may otherwise have not occurred, as well as others that are medically compatible for improved clinical outcomes.
"A more radical change is to allow compensation to be made to living donors in Singapore. At the time of writing, this amendment has already been passed in the parliament, and the MOH is working out compensation levels. Under the law, provision is made for direct costs incurred as a result of the donation, as well as indirect losses such as lost earnings and future expenses due to the donation. In order to control the financial incentive, all the reimbursements will be credited to the donors’ medical savings accounts instead of cash transfers."

HT: Joshua Gans and Sally Satel

Kidney exchange in Vienna

Here's an article discussing a simple paired exchange in Vienna, with plans to move soon to chains. It sounds like the last link in the chain of ideas and computer code led from Australia to Austria.

"The problem of incompatibility is solved by pairs (married couples, siblings, mother and child, friends, etc.) being selected using a new computing algorithm, which was developed in Australia and evaluated at the MedUni Vienna in a newly published pilot study, in which the organ donation is made possible in a "crossover." This means that each donor, whose kidney is not suitable for their own intended recipient, donates the organ to a stranger, the recipient in another pair and vice versa."

Directed deceased donation of organs for transplant. (Legal in U.S. but not yet in Europe.)

 It is legal in the U.S. for a deceased donor organ for transplant to be directed to a particular recipient, if the recipient is compatible (and otherwise the organs are allocated as in the usual way for nondirected deceased donation.)  Because compatibility is tricky, directed deceased donation (DDD) is rare (but deceased donor kidneys can potentially be used to start a deceased donor initiated chain of kidney exchange).

But in most of Europe, it turns out, DDD isn't legal. (!) Here's a paper by the European Society of Transplantation's European Platform on Ethical, Legal and Psychosocial Aspects of Organ Transplantation. It cautiously argues that maybe this ban is "one thought too many," and that the ban should be lifted so that carefully regulated DDD would be allowed to increase organ donation in Europe and save more lives.

"When is directed deceased donation justified? Practical, ethical, and legal issues," by David Shaw1,2 , Dale Gardiner3, Rutger Ploeg4, Anne Floden5,6, Jessie Cooper7, Alicia Pérez-Blanco8, Tineke Wind9, Lydia Dijkhuizen10, Nichon Jansen10 and Bernadette Haase-Kromwijk10; on behalf of the ESOT ELPAT Working Group on Deceased Donation, Journal of the Intensive Care Society, 2024.

Abstract: This paper explores whether directed deceased organ donation should be permitted, and if so under which conditions. While organ donation and allocation systems must be fair and transparent, might it be “one thought too many” to prevent directed donation within families? We proceed by providing a description of the medical and legal context, followed by identification of the main ethical issues involved in directed donation, and then explore these through a series of hypothetical cases similar to those encountered in practice. Ultimately, we set certain conditions under which directed deceased donation may be ethically acceptable. We restrict our discussion to the allocation of organs to recipients already on the waiting list.

"The persistent shortage of organs available for transplantation demands fair and objective allocation of the scarce available organs, based on preset transparent and regulated criteria. In most European countries, organs from deceased donors are allocated to patients on the organ waiting list by national Competent Authorities.3 The current worldwide norm is that organs donated after death are considered as an unconditional gift to the patients on the transplant waiting list according to the allocation system. This implies that donors (prior to their death), or their family members (after it), cannot determine to whom the available organs will be assigned, nor exclude any potential recipients.

...

"In a few countries, like the United States, United Kingdom, Japan, and recently Australia, directed deceased donation is possible in restricted cases, since national legislation does not prohibit it. In living donation however, directed donation is permitted in many countries, even when there is no genetic or emotional relationship between the donor and the intended recipient. This inconsistency between the living donation- and deceased donation system has been noted.4

"This paper explores whether directed deceased donation should be allowed, and if so under which conditions.

...

"The main argument against DDD is that this violates the  basic principle of an altruistic, unconditional gift to society; allowing DDD may turn out to be a “slippery slope” in the direction of conditional donation and discrimination against particular patient groups. Conditional donation could also reduce public support for the transplantation system, since it could reduce transparency and fairness of the system.

...

"What, then, are the conditions for ethical DDD at the present time?

1. DDD under strict conditions should not be prohibited by legislation or policy.

2. There must be evidence that the donor wanted or would have been willing to direct the organ to a particular family member or close friend.

3. The donor/family should generally not be able to  insist on only donating the organ intended for DDD; where other organs are transplantable there should be a willingness to donate other organs (at least one) to patients on the waiting list to preserve the societal altruistic aspect of donation and diminish the overall effect on the waiting list.

4. DDD should proceed only if there is no patient on the waiting list in extremely urgent need of an organ transplantation to avoid imminent death.

5. DDD should proceed only if there is a reasonable chance of successful transplantation.

6. The intended recipient should be on the waiting list or be under assessment for being included.

"If these conditions are met, the medical team should do their best to facilitate the wishes of the deceased patient and his/her family by enabling DDD to take place. Letting deceased donors direct their organs to loved ones under carefully controlled conditions could further enhance trust in organ donation and transplantation systems, and hence willingness to become a donor."